This gangliosidosis project will include two studies: 1) Continuation of LDN6713 Natural History of Hexosaminidase Deficiencies and Other Gangliosidoses for patients of all ages with a gangliosidosis disease; 2) Syner-G treatment regimen (synergistic enteral regimen for the gangliosidoses) for patients with infantile or juvenile forms of the gangliosidoses. Pediatric patients may simutaneously participate in both studies. The Syner-G regimen is a combination, multi-targeted combination therapy for treatment of the gangliosidoses, using FDA approved therapies that have demonstrated safety in children: miglustat, ketogenic diet to minimize gastrointestinal side effects of miglustat and optimize seizure management, and pyrimethamine for patients with mutations responsive to pyrimethamine. The infantile and juvenile forms of gangliosidosis are lethal during childhood. This gangliosidosis project provides a method for systematically gathering serial prospective, retrospective and natural history clinical data, including data on treatments tried by the patient. The ability to participate in the Syner-G treatment protocol, or other clinical treatment trials that may become available, allows for participation of patients who may otherwise be excluded from a natural history study. Specific Aim 1: To characterize and describe disease progression and heterogeneity in the gangliosidosis disorders. This natural history study (LDN 6713) seeks to develop quantitative methods to delineate disease progression for the gangliosidosis disorders (Tay-Sachs, Sandhoff, and GM1-gangliosidosis diseases) to better understand the natural history and heterogeneity of disease. Such quantitative methods will also be essential for evaluating any treatments that may become available in the future, such as gene therapy. Specific Aim 2: We hypothesize that a combination, multi-targeted therapy for pediatric gangliosidoses, using miglustat with the ketogenic diet?and pyrimethamine for patients with responsive mutations?will create synergisms that improve neurodevelopmental outcomes of therapy compared to data reported in previous natural history studies, and previous studies using monotherapy with miglustat.